Background and aims To elucidate the diversity of systemic lupus erythematosus (SLE), we stratified SLE patients based on immunophenotyping.

Methods Peripheral blood mononuclear cells were obtained from 80 active SLE patients (with one or more BILAG category A, or two or more BILAG category B). Circulating B, T and dendritic cells were defined based on flow cytometric analysis for human immune system termed ”the Human Immunology Project”. Based on these results, the immunophenotype was visualised by principal component analysis and SLE patients classified into subgroups by cluster analysis.

Results Principal component analysis indicated that the immunophenotype of active SLE patients was consistent with T and B cell axes. Among these correlations, Th17 and Treg cells were statistically close, and showed positive correlation (p<0.001). Furthermore, Tfh and Th1 cells were also statistically close, and showed positive correlation (p=0.04). The same pattern was also noted between Tfh and plasmablasts (p=0.02). Cluster analysis showed that SLE patients were divided into three subgroups (with high proportions of plasmablasts in all groups): patients did not show any characteristic features other than increased plasmablasts (T cell-independent group), patients with high percentage of Tfh cells (Tfh-dominant group), and patients with high proportions of activated Treg and memory Treg and low proportion of naïve Treg (Treg-dominant group).

Conclusions Our study indicates that SLE patients can be divided into three subgroups based on T cell heterogeneity. This heterogeneity should be taken into consideration not only in basic research but also in patient selection in clinical trials for development of new drugs.